Detox - Biotransformation Pathways
Healing From Mold Protocol #5 - From the "Step By Step Protocol" To Healing From Mold
Easy Peasy In A Nutshell: To support the bodies ability to transform biotoxins such as mycotoxins, endotoxins and non biologic toxins, you use nutritional support of the biotransformation system, and upregulate the metabolic enzymes needed for the detox pathways.
New Note: I wrote this article a long time ago, before people were discussing "cellular detox". Basically, what you are reading about here and my other articles on biotransformation is all about cellular detox at a level of great detail.
The Biotransformation/Detox System Is A Big Topic
To understand the biotransformation system is overwhelming for most people. Researchers are only just beginning to get a grasp of it. However, we know enough about this magnificent system to make use of the data in the process of getting well after being exposed to a water-damaged building. The biotranformation system is used by all cells of the body, but some cells like the liver, intestines, kidney, skin and lungs are busy beavers when it comes to transforming hormones, toxins and other substances to either transform them into something useful or remove them from the body. At least that is the idea of the system. It is basically a recycling, and trash removal system. However, sometimes the system does not work up to par and may make more toxic items or may not be able to remove items sufficiently due to genetics, or due to mycotoxins decreasing the activity and functionality of this beautiful system. Luckily, we can use nutrition through food and supplements, herbs, lifestyle changes and other healing modalities to support this biotransformation system and help increase the proper removal of mycotoxins and other toxins from the body.
When we don't have adequate glutathione (it is not a lone player, just an important player in the game) the mitochondria in our cells are overwhelmed by reactive oxyden species, and they start putting out danger repsonse signals as well as decreasing energy output which makes us tired. The singals they put out cause inflammation and havoc in the body. Therefore availability of glutathione and ability to recycle and use glutatione is very important.
At the above link you will find data on supporting methylation, glutathione conjugation, glucuronidation, sulfation, amino acid conjugation, and acetylation.
Or skip all that for the moment, and I will give you some basics on how we can support this process. Things that will help most, or many of the people who have been exposed and are sensitive to water-damaged buildings.
I am bringing up glutathione here as it is an amazing antioxidant that is used all through-out the many steps of cellular detox to keep the free radicals down. It is also necessary for glutathione conjugation which is one of the major detox processes in the body. Therefore, for anyone with a toxin issue, their bodies access to glutathione is very important. The first thing I usually have a person do after starting binders, or at the same time, is to take/enhance production of glutathione. Mycotoxins can interfere in the process of making and using glutathione, so simply supplying it, or N-acetyl-cysteine can be a big help in the beginning. The individual is often so sick by the time I work with them, that they are having trouble making enough glutathione, and rather than giving them the materials to make glutathione, I find they do better by simply replacing it for a while. (using forms that are more readily available) Additionally using methods to make more glutathione by providing a healthy diet, and using the supplement N-acetyl cysteine is beneficial, and is generally started as soon as possible. Be aware that glutathione is used by the body to detoxify itself of many things. So while you are increasing the ability to remove mycotoxins, you are also increasing removal of other toxins. This can be overwhelming to remove toxins from the tissues if done too fast. If the person reacts, back off and go slower. Reactions can also take place when a person is not consistent in taking supplements that remove toxins. So, they have to be taken on a set schedule.
An individual may need to support other conjugation activities such as acetylation, sulfation, methylation, glucuronidation, amino acid conjugation or even modulate CYP P450 enzyme activity depending on their genetics, signs, symptoms, and lab values. It is too much for me to go into detail on this page, but please look further into the biotransformation system, and how to support the various aspects of it.
I also have an entire page devoted to glutathione if you want to know more about it.
Glutathione And mycotoxins
Glutathione is necessary for both phase 1 and phase 2 of our detoxification pathways. Glutathione is necessary to remove many types of mycotoxins. The aflatoxin AFB1 can be metabolized by the Cytochrome P450 system to AFB1-8,9-epoxide (AFBO) which can become quite hazardous OR it can be excreted via the urine with the use of glutathione. Glutathione S-transferase is needed to conjugate AFBO and excrete it in the urine. If AFBO is not conjugated and excreted it can cause toxicity including cancer. This means both gluathione, and the enzyme used to conjugate the mycotoxin to glutathione, and glutathione have to be available.
Glutathione is A Master Antioxidant
Glutathione scavenges free radicals and helps regenerate other antioxidants such as vitamins C and E. Glutathione's antioxidant and detoxification abilities play a major role in the every day function of cells. Exposure to mycotoxins in humans requires the production of glutathione on an “as needed” basis. Research suggests that some of these mycotoxins themselves can decrease the formation of glutathione due to decreased gene expression of the enzymes needed to form glutathione. Mycotoxin-related compromise of glutathione production can result in an excess of oxidative stress as well as loss of toxin removal, both leading to tissue damage and systemic illness. This is why it is so important for people with mold associated illness to address low glutathione levels.
More Details on Glutathione
Glutathione is the star detoxifier in our body. It is a small protein composed of three amino acids - cysteine, glutamine, and glycine. It is synthesized in the body, but toxins, poor diet, and pollution, as well as stress, aging, trauma, infections and radiation all deplete glutathione levels. The sulfhydryl group (SH) of cysteine serves as a proton donor and is responsible for the biological activity of glutathione. Cysteine is the rate-limiting factor in cellular glutathione synthesis, since this amino acid is relatively rare in food. (cysteine is supplemented as N-acetyl cysteine or NAC) Normally glutathione is recycled in the body, except when the toxic load becomes too great, and in the case of mycotoxins they have been shown to decrease glutathione levels in the body.
Glutathione Conjugation And Glutathione S-Transferase
Glutathione conjugation is probably the most important detoxification pathway for industrial toxins and carcinogens and 60% of toxins excreted in the bile are excreted in this way. Glutathione conjugation also produces water-soluble mercaptates which are excreted via the kidneys.
Glutathione conjugation is a major route of memoval of mycotoxins. Glutathione is conjugated (attached) to the toxin and removed from the body through this process. The process requies an enzyme call glutathione transferase for this to take place. 33%-50% of people are missing normal GSTM1 (a gene) function that controls glutathione S-transferase. This gene needs to be available to enable adequate glutathione conjugation. So, these folks who are low in GSTM1 will have even more trouble conjugating mycotoxins with glutathione. If you have a 23 and me genetic test, look up rs366631, and if you are AA: GSTM1 =low/ lower enzyme activity likely, AG: GSTM1= normal enzyme activity is likely, GG :GSTM1= normal enzyme activity is likely. Now don't get worried if you are AA. We don't know everything there is to know about genetics and it is possible other aspects of your biotransformation system may help pick up slack. It even appears that GSTM2 may pick up part of the slack from a decreased activity of GSTM1. Lots of theories, and some studies, but waiting for some definitive reasearch.
Example of alternate detox pathways: The formation of glutathione conjugates, as well as glucuronide and sulfate conjugates to the mycotoxin called aflotoxin have been described in some animals, and many metabolites of aflatoxin can all undergo glucuronidation, and sulfation in addition to glutathione conjugation. Spirit has many pathways to the same destination.
Glutathione Supplements & Supporting Glutathione Production In The Body
Most forms of oral gluathione are digested by the body and otherwise not absorbed. However, even if they are digested, the amino acids can be reused by the body to make glutathione again, so not a total waste. However, it is more expensive than buying the amino acids cysteine, glutamine and glycine.
Acetyl-Glutathione is available from Allergy Research, and is a form of oral glutathione that is stable in the stomach and gastrointestinal tract and well absorbed. Liposomal glutathione is another form of glutathione with good absorption.
Nebulized (inhaled) glutathione is also used but should only be used under the care of a trained practitioner. It may cause a broncho-constriction reaction in some of your toxic patients.
Eating To Raise Glutathione
Anything that contains the sulfur amino acid called cysteine will be beneficial as it is the rate limiting amino acid necessary for making gluathione. Gluathione is made of the amino acids glycine, glutamine and cysteine.
Cysteine is an amino acid and can be found in most high protein foods such as meat, eggs, dairy, also good amounts in nuts and seeds, high in sunflower seeds, high in oats, and also in fish, dairy foods, legumes, asparagus, avacado, spinach.
Whey from making cheese or concentrated whey products are rich in cysteine: The whey protein needs to be bioactive and made from non-denatured proteins ("denaturing" refers to the breakdown of the normal protein structure). Use non-pasteurized, organic, non-denatured whey, or whey protein. I use to make cheese when I milked goats and had tons of whey. It can be added to smoothies, drank as is, or added to anything where you need moisture in a dish you are making. What is on the market is a concentrated whey product. This study found whey protein isolate increased plasma glutathione and total antioxidant capacity.
The body can also make cysteine, but does not always make enough. It is considered a semi-essential amino acid. Sulfur-rich foods are needed to make cysteine. Sulfur rich foods are onions, garlic, leeks, all cruciferous vegetables such a broccoli, collards, cabbage, brussel sprouts, kale, cauliflower, kohlrabi, watercress, etc. The glucosinolates such as glucoraphanin in the cruciferous vegetables is changed by myorsinase (in the plant or made by colon bacteria) to sulforaphane that is then conjugated with our bodies glutathione and ultimately made into a sulforaphane N-acetlycysteine using our bodies glutathione, and may exhibit goitrogenic or antithyroid activity. Although we are providing sulfurs by eating Cruciferae plants (mustard family), we are also using our glutathione in the metabolism of the plant materials. Is this an issue? I really can't say.
Health TIP or Side Rant On Sensitivity To Cruciferae Plants - Depending on your point of view
I can tell you that I have had some very sensitive "moldy people" tell me that they react to eating Cruciferae plants. Glutathione conjugation is used to process these plants in the body. The fact that they are using glutathione to metabolize these plants could be one possible reason why. Although, it would not bother most people eating the plants in moderation, for someone with little glutathione available, it might be just enough to push them over the edge. It could even be that the upregulation of glutathione production and glutathione conjugation could be causing a reaction due to the increased detoxing, and therefore a possible detox reaction.
However, another reason could be the fact that these plants supply a lot of sulfur, and sulfur gets turned into sulfite in the body before it is changed into the sulfate that we use for various necessary processes. The enzyme sulfite oxidase is needed to catalyse the metabolic detoxification of sulfite to sulfate in the body within the intermembrane space of the mitochondria who make all our energy. Molybdenum is needed for sulfite oxidase to work correctly. If a person is low in molybdenum this biotransformation of sulfite (form that could cause an issue if it builds up) to sulfate (the form we need to use) will not take place efficiently and sulfite will build up, and may cause a reaction. (Glyphosate, the active ingredient in RoundUp can bind molybdenum, making it unavailable.) Another, third possibility would be the idea that some people may have a Cystathionine Beta synthase (CBS) mutation, which would keep homoceysteine from going through the transulfuration cycle and ever having the possibility of becoming glutathione. This could theroretically create a back-up, and could increase homocysteine and other precursors to homocysteine. So, these are three possible reasons for reactions in these individuals sensitive to Cruciferae plants. If these same people have trouble with the biotransformation process called sulfation (requires sulfur) it is likely that their issues is a problem changing sulfite into sulfate and besides considering their molybdenum and B2 level, I would have them take Epsom salt bathsa as an immediate method to enhance their sulfate lelve which is needed for the important conjugation process of sulfation.
I am including a diagram with the transulfuration cycle and how sulfite is changed to sulfate, see below.
Everything should be done in moderation as always, even eating Kale.
Many people on the web claim that Crucifereae plants give us cysteine or glutathione, but from the research studies I read, it is evident they give us sulfur to make cysteine, or in the process of conjugating with our glutathione, and undergoing more metabolic processes, that our glutathione is broken down to make cysteine. I can't find the data that shows these plants contain cysteine or glutathione. If anyone has a research article showing glutathione, or cysteine are actually in Cruciferae plants, please send it to me at the contact email at the top of the page.
The Cruciferae And Glutathione-S-transferase.
The Cruciferae plants appear to ramp up production of glutathion-S-transferase. This is not unusual when a plant uses a biotransformation pathway for that pathways activity to be increased if the plant is consumed on a continual basis, but usually not so much as to use the enzymes up as might happen with an environmental toxin (unless you are the sensitive person above in the "Tip"). Cruciferae plant metabolites are conjugated in the body by the use of glutathione-S-transferase inducing glutathione conjugation to the plant substances, so they might be inducers of glutathione-S-transferase production, and ultimately increase the ability of glutathione to conjugate with toxins. Studies in animals and humans appear to support this thought. This means that the net effect of eating the Cruciferous vegetables over time would be a beneficial one as far as glutathione conjugation and removal of mycotoxins.
Although cysteine is the rate limiting amino acid, remember that glutathione is also made from gluatamine and glycine. Additionally, selenium helps both produce and recycle glutathione. Selenium content in food depends on the soil that food is grown in. Some areas are high in selenium and some low. However, brazil nuts, sunflower seeds, oatmeal , tuna, turkey, beef, chicken breast, eggs and brown rice are possible sources of selenium.
Some Additional Thoughts About Cruciferae Plants and Glutathione
Sulforaphanes (glucoraphanin-derived isothiocyanate) ability to reduce oxidative stress in different settings is linked to activation of the nuclear factor E2-related factor 2 (Nrf2)-dependent pathway. I think we will find these Cruciferous veggies have a modulating effect when eaten in some moderate amount. It does appear this way in the studies. More about this below.
Raising Nrf2: Nrf2 increases tissue glutathione levels and also controls the formation of the glutathione s-transferases. So, anything that enhance Nrf2 will be supportive of glutathione, glutathione conjugation and moving mycotoxins out of the body.
HEALTH TIP - Also Another Reason Someone Might React To Cruciferous Vegetables
Isothiocyanates are irritating to mucous membranes and not readily consumed in sufficient quantities to be toxic. However, if they are consumed as glucosinolates and then hydrolyzed to isothiocyanates via mastication or in the gut, they are thought to have powerful antithyroid effects and interfere with the synthesis of necessary thyroid hormones. It has been thought that cooking the plants stops this formation due to damage of the myrosinase but now we realize that we have bacteria that make myrosinase, and the glucosinolates are still hydrolyzed in the colon with these bacterial produced myrosinase. It is also known that glucosinolates are damaged during cooking, The amount lost in the cooking process is variable but can be from 20-30% in steaming or boiling 10-15 minutes and 45-60% in pressure cooking. One study showed an increase in them from steaming. So, if you want more glucosinolates, steaming sounds like a good idea. If you want to lower them, get that pressure cooker out. The studies have varied results with cooking and you can read more about it here.
In animal studies they have identified that the animals can tolerate 10% of their diet being rapeseed (Cruciferae plant that also contains glucosinolates) before they have symptoms of poisoning from the glucosinolates.
Many studies have shown that consumption of Cruciferae vegetables is associated with anticarcinogenic effects and other beneficial biological activities associated with their breakdown products. Studies have additionally described the assimilation and metabolism of both glucosinolates and their derivatives, however, we lack the knowledge of detailed mechanisms associated with these activities.
Supplements to Support glutathione formation And Recycling Of Glutathione
Glutathione production can be supported by n-acetyl cysteine, glutamine, glycine, Vitamins C and E, selenium, magnesium, zinc, B vitamins, vitamin D and alpha-lipoic acid.
Herbs to increase Glutathione
- Turmeric - Curcuma longa
- Milk thistle - Silybum marianum
- Cinnamonum - Cinnamon (human study did not specify species)
- Cordyceps - Coryceps sinensis/militaris (okay, a mushroom and not technically an herb)
- Gotu kola - Centella asiatica
Eating to Raise Glutathione S-transferase (GST) - to enhance glutathione conjugation
Studies have found Cruciferous vegetables can enhance Glutathione S-transferase (GST). One study found a significant increase in the amount of serum GST and its GST activity when GSTM1-null individuals, especially women ate a moderate diet of Cruciferae plants. It appears that being a GSTM1-null or listed as AA on a "23 and Me" report (people who are thought to have low GST activity - although other genes may make up for it) means a Cruciferae diet might enhance your ability to make GST. Yipee for those folks.
Whey (cheese making by-product) from non-pasteurized and organic animals. Want precursors from whey as follows: Serum albumin, alpha lactoalbumin, lactoferin, beta lactoglobulin. These globular proteins are high in cysteine and cysteine residues and can be manufactured into glutathione.
Anything that enhances Nrf2 will increase glutahtione and GST. In a study comparing four NRF2 activators, it was found that R-α-Lipoic acid, sulforaphane and Polygonum cuspidatum extract containing 50% resveratrol increased astroglial release of glutathione.
Sulforaphane (lots in fresh broccoli/sprouts) produced the best effect. It increased glutathione by up to 2.4-fold. Polygonum increased glutathione up to 1.6-fold, and lipoic acid (1.4-fold).
Supplements to Raise Glutathione S-transferase - to enhance glutathione conjugation
S-Adenylsyl methionine (SamE or SAM) in studies with mice - Methionine feeds into a cycle that includes preliminary steps to make glutathione. I have an article on the methionine/methylation cycle on this website.
Cardamom - Elettaria cardamomum upregulated glutathione-S-transferase and glutathione peroxidase in mice.
Green Tea polyphenols significantly enhance GST levels and activity in human study.
Additional Methods to Support Glutathione or Glutathione Conjugation
Anything that reduces stress will help preserve glutathione. Studies have shown that relaxation techniques change gene expression and enhance glutathione levels.
- Meditation and prayer enhance glutathione
- Biofeedback practices enhance glutathione
- Yoga enhances glutathione
- Supporting restful sleep will help support glutathione levels
I think you get the picture, you choose your choice of relaxing activity.
Exercise also boosts levels.
I realize that we only covered one aspect of the biotransformation/detox pathways in covering glutathione and glutathione conjugation. I suggest you look further into other parst of the biotransformation pathways by starting at this article.
Next, read the article on "Healing Inflammation From Mold Exposure".
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